Visual loss in acute optic neuritis is typically attributed to axonal conduction block due to inflammatory demyelination, but the mechanisms remain unclear. Recent research has highlighted tissue hypoxia as an important cause of neurological deficits and tissue damage in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) and, here, we examine whether the optic nerves are hypoxic in experimental optic neuritis induced in Dark Agouti rats. At both the first and second peaks of disease expression, inflamed optic nerves labelled significantly for tissue hypoxia (namely, positive for hypoxia inducible factor-1α (HIF1α) and intravenously administered pimonidazole). Acutely inflamed nerves were also labelled significantly for innate markers of oxidative and nitrative stress and damage, including superoxide, nitric oxide and 3-nitrotyrosine. The density and diameter of capillaries were also increased. We conclude that in acute optic neuritis, the optic nerves are hypoxic and come under oxidative and nitrative stress and damage. Tissue hypoxia can cause mitochondrial failure and thus explains visual loss due to axonal conduction block. Tissue hypoxia can also induce a damaging oxidative and nitrative environment. The findings indicate that treatment to prevent tissue hypoxia in acute optic neuritis may help to restore vision and protect from damaging reactive oxygen and nitrogen species.
- MeSH
- encefalomyelitida autoimunitní experimentální * metabolismus MeSH
- hypoxie metabolismus MeSH
- imunologické faktory metabolismus MeSH
- krysa rodu rattus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nervus opticus metabolismus MeSH
- zánět zrakového nervu * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: Optic neuritis (ON) is an inflammatory demyelinating disorder of the optic nerve, which can be the first manifestation of multiple sclerosis (MS). The main goal was to assess changes in the retinal nerve fibre layer (RNFL) and in retinal oxygen saturation [arterial (AS), venous (VS) and arterio-venous (A-V) difference] in the affected and unaffected eye. METHODS: Fifty patients with ON due to MS within 3 months of onset of symptoms were enrolled (17 males, mean age 35.3). All patients were examined at baseline (V1) and after 6 months (V2) using optical coherence tomography (OCT) to get RNFL values; automatic retinal oximetry to obtain saturation values; and ultrasound to exclude arterial stenosis, and orbital colour Doppler imaging was performed in the ophthalmic artery. RESULTS: At V1, AS was significantly increased in affected eye compared to unaffected eye (99.5% versus 98.0%, p = 0.03). Significant decrease in A-V difference from baseline was detected in both eyes for ON eye: 32.0% versus 29.0%, p = 0.004; for fellow eye: 31.4% versus 30.0%, p = 0.04. We did not observe any changes in retinal vessel diameter. There were no changes observed in blood flow in ophthalmic artery. At V1, there were no significant differences in RNFL, and significant loss of RNFL was confirmed in the affected eye at V2 (95 μm versus 86 μm, p = 0.0002) and in comparison with the fellow eye (86 μm versus 94 μm, p = 0.0002). There were no correlations between RNFL and saturation values at V1, although at V2, there was a negative correlation between the RNFL and AS (Spearman's rho = -0.480, p = 0.003) and between the RNFL and VS (rho = -0.620, p = 0.00007). CONCLUSION: Retinal oximetry is altered in both eyes in MS patients with unilateral ON. During the course of the disease, the retinal oxygen consumption decreases to a different degree in each eye and this change is not completely followed by changes in the RNFL thickness, suggesting either sub-clinical ON or systemic effects in the clinically unaffected eye. Since this is the first and initial longitudinal evaluation of the saturation changes in MS patients, the clinical value of these findings needs to be deeper evaluated in the future studies.
- MeSH
- časové faktory MeSH
- dospělí MeSH
- kyslík metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- následné studie MeSH
- nervová vlákna MeSH
- nervus opticus metabolismus patologie MeSH
- optická koherentní tomografie metody MeSH
- oxymetrie MeSH
- prospektivní studie MeSH
- retinální gangliové buňky metabolismus patologie MeSH
- roztroušená skleróza komplikace metabolismus MeSH
- spotřeba kyslíku * MeSH
- zánět zrakového nervu diagnóza etiologie metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
